Response to Bastard et al.

Bastard et al. (1,2) have examined the correlation between the oral glucose tolerance test (OGTT)-derived muscle insulin resistance index and the total glucose disposal divided by the steady-state plasma insulin concentration (TGD/SSPI) during the euglycemic insulin clamp in obese postmenopausal women and reported a lower correlation coefficient (2) compared with that reported earlier in a more heterogeneous population (3). Further, the correlation between the OGTT-derived muscle insulin resistance index (3) and TGD/SSPI was not significantly different from the correlation with other OGTT-derived insulin sensitivity indexes, including a novel index proposed by Bastard et al. (2). Bastard et al. attributed the discrepancy to the fact that the population they tested the indexes in is more homogenous than the one in which we developed the insulin resistance index.

Indeed, the variability in insulin sensitivity among individuals is expected to be smaller in any homogeneous population, and the correlation between the insulin clamp and OGTT-derived insulin resistance index would be weaker because of the narrow range of the variable of interest (i.e., insulin-stimulated glucose disposal). For example, if we limit the analysis in our population to subjects with a BMI >30 kg/m2 (i.e., a group expected to be very insulin resistant), the correlation coefficient between the muscle insulin sensitivity index derived from the OGTT and the TGD/SSPI declines from 0.78 to 0.61. Because most of these obese subjects are very insulin resistant, the range of their insulin sensitivity values is much narrower than the whole group. For example, the range was 0.056–2.58 in the obese subgroup compared with 0.048–4.77 in the whole group. Therefore, it is likely that the reduced correlation observed by Bastard et al. in obese postmenopausal women is related to the narrow range of insulin sensitivity in the group of obese postmenopausal women.

Moreover, the correlation between the muscle insulin sensitivity index and the hepatic insulin resistance index (measured as hepatic glucose production × fasting plasma insulin) was significantly less than the correlation with TGD/SSPI, suggesting that this index has some selectivity over the other indexes in detecting insulin resistance in skeletal muscle. In our dataset, the correlation between the insulin sensitivity index proposed by Bastard et al. and hepatic glucose production × fasting plasma insulin was not significantly different from the correlation with TGD/SSPI (0.43 and 0.57, respectively, P = 0.19).